Drug abuse among young women is on the rise, with a recent report stating that 56 percent of cocaine users ages 12-17 are women. Women escalate more rapidly through all stages of drug addiction as compared to men, making them especially vulnerable to the deleterious effects of cocaine. Pharmacological treatments for cocaine abuse that are effective in men, such as naltrexone, are ineffective in females or even increase drug use. While it may be possible to develop gender-specific pharmacologic treatments for cocaine abuse in women, non-pharmacologic treatments are also needed. Research in laboratory animals and survey research with humans has indicated a potentially protective effect of the formation of strong social bonds with regards to drug abuse. The strongest social bond formed in rats is the mother-infant bond. Following the rearing of offspring, female rats demonstrate improved learning and memory, increased exploration and foraging ability, attenuated age-related decreases in cognitive function, and decreased neurobehavioral stress and fear responses, even after the offspring have been weaned. These beneficial alterations have been shown to persist for months after the offspring have left the nest, indicating relatively permanent neural reorganization. Importantly, these benefits of maternal behavior occur in nulliparous foster mothers and males that have been induced to act maternally, indicating that pregnancy and parturition are not required for these benefits to be seen. Both drugs of abuse and formation of social bonds induce changes in the neuronal targets of the mesolimbic dopamine pathway, in particular in the nucleus accumbens and striatum. When attachment to a conspecific or drug of abuse is induced, the ability of this neural system to form an attachment to alternate goals is reduced. So, male prairie voles that have pair-bonded with a female do not develop a conditioned place preference to a low dose of amphetamine, while non-bonded males do. Likewise, male voles that have exhibited sensitization to amphetamine do not readily form a pair-bond when presented with a female. Preliminary data from our laboratory have shown that primiparous females exhibit less behavioral sensitization with repeated cocaine administration than do nulliparous age-matched females. The experiments proposed here will test the hypothesis that beneficial effects of social bond formation during the maternal experience of caring for young (whether the female is parturient or not) can protect females from susceptibility for drug abuse. Specifically, experiments will examine if caring for young can affect cocaine self-administration behavior (i.e., the rate of acquisition, the motivation to self-administer cocaine, continuation of responding during periods of non-reinforcement, and persistence to take drug in the face of aversive outcomes), and/or the animals'endogenous response to repeated cocaine exposure using a behavioral sensitization paradigm and in vivo microdialysis. PUBLIC HEALTH RELEVANCE: The experiments proposed here will test the hypothesis that beneficial effects of social bond formation during the maternal experience of caring for young (whether the female is parturient or not) can protect females from susceptibility for drug abuse. Data generated from these experiments will provide a first step towards delineating neurobiological/neurobehavioral mechanisms that may attenuate drug taking in females and lead to identification of new methods to help treat women who are at risk for drug addiction.